CN1709865A - High-optical-purity chiral beta-alkamine compound, preparing method and its use - Google Patents

High-optical-purity chiral beta-alkamine compound, preparing method and its use Download PDF

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CN1709865A
CN1709865A CN 200510027249 CN200510027249A CN1709865A CN 1709865 A CN1709865 A CN 1709865A CN 200510027249 CN200510027249 CN 200510027249 CN 200510027249 A CN200510027249 A CN 200510027249A CN 1709865 A CN1709865 A CN 1709865A
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CN1281582C (en
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徐明华
林国强
钟羽武
董一洲
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

This invention involves high optical purity chiral beta-amino alcohols compounds, its method of preparation and function. The structure formula of chirality beta-amino alcohols compounds is (A) or (A'). Thereinto, R1 is straight-chain and branched chain or aryl alkyl that carbon atomicity is 1-16,or naphthene that carbon atomicity is 3-6; R2 is straight-chain and branched chain or aryl alkyl that carbon atomicity is 1-12, naphthene that carbon atomicity is 3-6, or phenyl replaced by R3 or R4; R3 or R4 is hydrogen, alkyl that carbon atomicity is 1-6, halogen, alkoxy that carbon atomicity is 1-5,or OCOR5; mentioned halogen is F, Cl or Br; R5 is alkyl that carbon atomicity is 1-6.This compound can get rid of chirality tertiary butyl sulphinyl further and get high optical purity chirality beta-amino alcohols compounds.

Description

High-optical-purity chiral beta-alkamine compound, preparation method and its usage
Technical field
The present invention relates to chiral beta-alkamine compound, new synthetic method, and their purposes.
Background technology
The chirality beta-alkamine is the very useful compound of a class, much has physiologically active.They are the important synthons in some drug molecules and the natural product molecule synthesis, also are important chiral ligand and chirality assistant agent in a lot of asymmetric reactions.((a) Lee, H.-S.; Kang, S.H.Synlett 2004,1673. (b) Ager, D.J.; Prakash, I.; Sehaad, D.R.Chem.Rev.1996,96,835. (c) Pu, L; Yu, H.-B.Chem.Rev.2001,101,757.) therefore, the high-efficiency synthesis method of development preparation chirality beta-alkamine all is subjected to various countries organic chemists' attention always.(Bergmeier, S.C.Tetrahedron 2000,56, and 2561.) theoretically, the tetramethyl ethylene ketone of aldehyde and imines (Pinacol) class cross-coupling is the most convenient of preparation beta-alkamine compound, direct method.But in fact owing to be difficult to suppress or avoid self linked reaction of under reaction conditions aldehyde or imines, the general difficult cross-coupling of realizing aldehyde and imines is said nothing of the stereoselectivity of control reaction.That is to say that the chemo-selective that will obtain and stereoselectivity are very difficult, especially stereoselectivity.At present the example of these class methods of bibliographical information is also few, and mostly only is used for beta-alkamine compound synthetic of some racemizations.((a) Roskamp, E.J.; Pedersen, S.F; J.Am.Chem.Soc.1987,109,6551. (b) Shono, T.; Kise, N.; Fujimoto, T.Tetrahedron Lett.1991,32,525. (c) Guijarro, D.; Yus, M.Tetrahedron 1993,49,7761. (d) Machrouchi, F.; Namy, J.L.Tetrahedron Lett.1999,40,1315. (e) Shimizu, M.; Iwata, A.; Makino, H.Synlett 2002,1538.) comparatively successful example is the tricarbonyl chromium that utilizes planar chiral of development in recent years or the cross-coupling of ferrocene-containing compound, but the scope of application of reaction is very narrow, only is suitable for a handful of aromatic substrate and ferrocene substrate.((a) Taniguchi, N.; Uemura, M.J.Am.Chem.Soc.2000,122,8301. (b) Tanaka, Y.; Taniguchi, N.; Uemura, M.Org.Lett.2002,4,835. (c) Tanaka, Y; Taniguchi, N.; Kimura, T.; Uemura, M.J.Org.Chem.2002,67,9227.) therefore, the method that develops new high-efficient simple ground synthesis of chiral beta-alkamine and derivative thereof more and more receives chemists' concern.
Summary of the invention
The purpose of this invention is to provide a kind of high-optical-purity chiral beta-alkamine compound;
Another object of the present invention provides a kind of high-optical-purity chiral beta-alkamine compound of preparing
Novel synthesis;
Purpose of the present invention also provides a kind of purposes for preparing high-optical-purity chiral beta-amino alcohol compound.
High-optical-purity chiral beta-alkamine compound of the present invention has following structural formula:
Perhaps
Figure A20051002724900042
R wherein 1Be the fatty substituting group of non-fragrance, R 2Then can be aromatic substituent, alkyl substituent that also can right and wrong fragrance, the fatty substituting group of non-fragrance described here be straight chained alkyl, have alkyl, the cycloalkyl of side chain or aryl; That is to say that reaction substrate aldehyde 1 is non-aromatic aldehyde, chirality N-tertiary butyl sulfinyl aldimine 2 then can be fragrance or fatty.Specifically, R 1=C 1-16Straight chain, have the alkyl of side chain or aryl or C 3-6Cycloalkyl; R 2=C 1-12Straight chain, have the alkyl of side chain or aryl or C 3-6Cycloalkyl, or R 3Or R 4The phenyl that replaces; R 3Or R 4=H, C 1-6Alkyl, halogen, C 1-6Alkoxyl group, or OCOR 5Described halogen is F, Cl or Br; R 5=C 1-6Alkyl.
Novel synthesis of the present invention can be represented by following type reaction formula:
Figure A20051002724900043
R wherein 1=C 1-16Straight chain, have the alkyl of side chain or aryl or C 3-6Cycloalkyl; R 2=C 1-12Straight chain, have the alkyl of side chain or aryl or C 3-6Cycloalkyl, or R 3Or R 4The phenyl that replaces; R 3Or R 4=H, C 1-6Alkyl, halogen, C 1-6Alkoxyl group, or OCOR 5Described halogen is F, Cl or Br; R 5=C 1-6Alkyl.
But novel synthesis classified description of the present invention is as follows:
Committed step of the present invention is that the cross-coupling reaction of aldehyde 1 and optically pure chirality N-tertiary butyl sulfinyl aldimine 2 generates chiral beta-alkamine compound 3.With samarium diodide (SmI 2) as reaction reagent, in organic solvent tetrahydrofuran (THF) and the trimethyl carbinol ( tBuOH) or under the existence of methyl alcohol (MeOH) ,-78 ℃～-10 ℃ is temperature of reaction, react and do not wait in 1 to 20 hour, can obtain structural formula with the productive rate of 60-99% and be
Figure A20051002724900051
Perhaps
Figure A20051002724900052
Chiral beta-alkamine compound 3, R wherein 1And R 2As previously mentioned.In this reaction, when the consumption of N-tertiary butyl sulfinyl aldimine 2 was 1.0 mmoles, the consumption of aldehyde 1 was the 1.0-3.0 mmole, samarium diodide (SmI 2) consumption is the 1.5-2.2 mmole, the trimethyl carbinol ( tBuOH) or the consumption of methyl alcohol (MeOH) also be the 1.5-2.2 mmole.
In the above-mentioned reaction, the diastereoselectivity ratio (dr) of resulting chiral beta-alkamine compound 3 can reach 88: 12～and＞99: 1.
The chirality beta-alkamine derivative 3 (HCl, the CF under acidic conditions that obtain among the present invention 3COOH etc.) reaction just can remove chirality N-tertiary butyl sulfinyl in 1-10 hour easily, received the chirality beta-alkamine
Figure A20051002724900053
Further carry out the acetyl glycosylation reaction, can obtain its acetyl derivative with the yield of 85-99%
Figure A20051002724900054
The enantioselectivity of reaction is to record with chirality HPLC by its acetyl derivative, reaches 90～99%ee.
Concrete experimental result is listed as follows:
The cross-coupling reaction of table 1, samarium diodide inductive aldehyde and chirality N-tertiary butyl sulfenimide
Numbering R 1 ????R 2 Product 3 Yield (%) ??dr ??ee(％)
?1 ?2 ?3 ?4 ?5 ?6 ?7 ?8 ?9 ?10 ?11 ?12 ?13 ?14 ?15 ?16 4-CH 3C 6H 44-CH 3C 6H 44-CH 3C 6H 44-CH 3C 6H 44-CH 3C 6H 4Ph 4-FC 6H 44-ClC 6H 44-BrC 6H 44-AcOC 6H 44-CH 3OC 6H 43，4-(MeO) 2C 6H 32，4-(MeO) 2C 6H 3 iPr PhCH 2CH 2CH 3(CH 2) 4 ??? iPr ????C 6H 11????(Et) 2CH ????n-C 5H 11????PhGH 2CH 2??? iPr ??? iPr ??? iPr ??? iPr ??? iPr ??? iPr ??? 1Pr ??? iPr ??? iPr ??? iPr ??? iPr ????3a ????3b ????3c ????3d ????3e ????3f ????3g ????3h ????3i ????3j ????3k ????3l ????3m ????3n ????3o ????3p ????92 ????90 ????73 ????90 ????95 ????86 ????89 ????71 ????70 ????82 ????84 ????90 ????73 ????88 ????87 ????95 ??＞99∶1 ??99∶1 ??＞99∶1 ??91∶9 ??88∶12 ??99∶1 ??98∶2 ??99∶1 ??＞99∶1 ??＞99∶1 ??＞99∶1 ??＞99∶1 ??＞99∶1 ??＞99∶1 ??96∶4 ??98∶2 ??98 ??＞99 ??99 ??95 ??95 ??97 ??＞99 ??98 ??＞99 ??＞99 ??＞99 ??＞99 ??＞99 ??98 ??＞99 ??97
Method of the present invention is carried out cross-coupling reaction with aldehyde and chirality N-tertiary butyl sulfinyl aldimine under the samarium diodide condition, not only easy, direct, and efficient.Here, the chirality N-tertiary butyl sulfinyl in the imines is the key of inducing the linked reaction highly-solid selectively.Because the wide application range of substrates of reaction, the diastereoselectivity ratio (dr) and the enantioselectivity (ee) of product are very high, therefore have good practicability, are a kind of fabulous methods for preparing high-optical-purity chiral beta-alkamine compound.The high-optical-purity chiral beta-alkamine compound that obtains can be advantageously used in the preparation of high-optical-purity chiral beta-amino alcohol.
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1
3a's is synthetic
In 25mL Schlenk bottle, with 1.0mmol samarium diodide (SmI 2) tetrahydrofuran (THF) (THF) solution (5mL) be cooled to-78 ℃, drip corresponding (the R)-chiral imines of 0.5mmol, 6mL tetrahydrofuran (THF) (THF) solution of the corresponding aldehyde of 1.0mmol and the 1.0mmol trimethyl carbinol, reacted 4 hours, the cancellation of 5mL saturated aqueous sodium thiosulfate, ethyl acetate extraction, saturated common salt water washing, anhydrous sodium sulfate drying, concentrate, purification by silica gel column chromatography obtains corresponding cross-coupling product 3a fast, productive rate 92%, experimental result sees table 1 for details.
3a[α] D 20＝-48.2°(c0.80，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.94(d，3H，J＝5.1Hz)，0.96(d，3H，J＝5.1Hz)，1.22(s，9H)，1.49(m，1H)，2.07(br，1H)，2.33(s，3H)，3.61(br，1H)，3.68(d，1H，J＝5.7Hz)，4.45(t，1H，J＝4.8Hz)，7.14(d，2H，J＝8.1Hz)，7.29(d，2H，J＝8.1Hz)；FT-IR(KBr，cm -1)：3346，1463，1031；ESI-MS(m/z，％)：298.3(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ18.26，19.32，21.09，22.57，30.17，55.96，60.42，78.82，128.39，129.31，135.39，137.85；HRMS?for?C 16H 27NO 2SNa(M ++Na)：calcd.320.1655，found：320.1634.
Embodiment 2
3b's is synthetic
Operate the same, productive rate 90%.
Figure A20051002724900071
3b[a] D 20＝-53.8°(c1.35，CHCl 3). 1H?NMR(300MHz，CDCl 3)：δ1.24(d，6H，J＝7.2Hz)，1.24-1.26(m，4H)，1.72-1.90(m，6H)，2.34(s，3H)，3.66(dd，1H，J＝4.2，7.2Hz)，3.77(d，1H，J＝5.7Hz)，4.47(t，1H，J＝4.9Hz)，7.15(d，2H，J＝8.0Hz)，7.28(d，2H，J＝8.0Hz)；FT-IR(KBr，cm -1)：3346，1463，1031；ESI-MS(m/z，％)：338(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ21.12，22.63，25.59，25.86，26.33，28.27，29.55，39.67，56.03，60.00，78.05，128.38，129.36，135.56，137.80；HRMS?for?C19H31NO2SNa(M ++Na)：calcd.360.1967，found：360.1974.
Embodiment 3
3c's is synthetic
Operate the same, productive rate 73%.
Figure A20051002724900072
3c[α] D 20＝-36.0°(c1.05，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.85(q，6H，J＝3.0Hz)，1.19(s，9H)，1.21-1.56(m，5H)，1.76(br，1H)，2.33(s，3H)，3.64(d，1H，J＝5.4Hz)，3.85(br，1H，)，4.45(t，1H，J＝5.4Hz)，7.15(d，2H，J＝8.1Hz)，7.28(d，2H，J＝8.1Hz)；FT-IR(KBr，cm -1)：3370，3336，2967，1513，1466，1033；ESI-MS(m/z，％)：326.3(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ10.50，10.61，20.01，21.10，21.29，22.59，41.69，56.03，60.42，74.90，128.30，129.40，135.77，137.86；HRMS?for?C 18H 31NO 2SNa(M ++Na)：calcd.348.1968，found：348.1989.
Embodiment 4
3d's is synthetic
Operate the same, productive rate 90%.
Figure A20051002724900073
3d[α] D 20＝-30.2°(c0.30，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.86(t，3H，J＝6.9Hz)，1.12-1.20(m，2H)，1.28(s，9H)，1.29-1.36(m，6H)，2.34(s，3H)，3.78(s，1H)，3.96(t，1H，J＝4.5
Hz)，4.35(dd，1H，J＝3.6，5.4Hz)，7.15(d，1H，J＝7.8Hz)，7.23(d，2H，J＝7.8Hz)；FT-IR(KBr，cm -1)：3300，2959，2919，1462，1046；ESI-MS(m/z，％)：326.2(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ13.90，21.00，22.46，22.58，25.51，31.64，33.29，56.13，62.17，73.60，128.11，129.07，135.23，137.50；HRMS?for?C 18H 32NO 2S(M ++H)：calcd.326.2148，found：326.2144.
Embodiment 5
3e's is synthetic
Operate the same, productive rate 95%.
Figure A20051002724900081
3e[α] D 20＝-53.8°(c1.35，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ1.18(s，1H)，1.22(s，8H)，1.23-1.26(m，1.4H)，1.48-1.50(m，1.4H)，2.33(s，3H)，2.78-2.83(m，2H)，2.64-2.67(m，2H)，3.95(s，1H)，3.99(d，1H，J＝6.3Hz)，4.37(dd，1H，J＝5.1，9.6Hz)，7.13-7.28(m，9H)；FT-IR(KBr，cm -1)：3377，3024，2857，1047，1038；ESI-MS(m/z，％)：360(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ21.01，22.62，32.17，35.10，56.21，62.26，73.02，125.76，128.09，128.22，128.27，128.33，129.19，135.10，137.67，141.70；HRMS?for?C 21H 30NO 2SNa(M ++Na)：calcd.360.1992，found：360.1998.
Embodiment 6
3f's is synthetic
Operate the same, productive rate 86%.
Figure A20051002724900082
3f[α] D 20＝-51.3°(c0.65，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.94(t，6H，J＝6.9Hz)，1.21(s，9H)，1.48(m，1H)，2.00(br，1H)，3.63(br，1H)，3.74(d，1H，J＝5.7Hz)，4.49(dd，1H，J＝5.7，4.5Hz)，7.31-7.43(m，5H)；FT-IR(KBr，cm -1)：3410，3327，2956，1475，1041，699；ESI-MS(m/z，％)：284.2(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ18.29，19.33，22.59，30.17，56.05，60.61，78.85，128.19，128.52，128.64，138.40；HRMS?for?C15H25NO2SNa(M ++Na)：calcd.306.1498，found：306.1515.
Embodiment 7
3g's is synthetic
Operate the same, productive rate 89%.
3g[α] D 20＝-42.1°(c1.05，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.94(d，3H，J＝1.5Hz)，0.96(d，3H，J＝1.5Hz)，1.22(s，9H)，1.24-1.27(m，1H)，2.12(d，1H，J＝2.1Hz)，3.61(dd，1H，J＝3.9，7.8Hz)，3.70(d，1H，J＝5.7Hz)，4.48(dd，1H，J＝5.7，9.3Hz)，7.05(d，2H，J＝18.1Hz)，7.42(d，2H，J＝18.1Hz)；FT-IR(KBr，cm -1)：2961，2872，1604，1511，1048；ESI-MS(m/z，％)：302.2(M ++H)； 13CNMR(75MHz，CDCl 3)：δ18.34，19.15，22.49，30.21，56.05，60.01，78.99，115.19，115.47，130.25，130.35，134.39，134.44，160.69，163.96；HRMS?for?C 15H 25NO 2SF(M ++H)：calcd.302.1584，found：302.1583.
Embodiment 8
3h's is synthetic
Operate the same, productive rate 71%.
Figure A20051002724900092
3h[α] D 20＝-35.8°(c0.80，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.94(d，6H，J＝6.6Hz)，1.21(s，9H)，1.45(m，1H)，2.27(br，1H)，3.60(m，1H)，3.81(m，1H)，4.44(m，1H)，7.30(dd，2H，J＝2.4，6.6Hz)，7.36(dd，2H，J＝2.4，6.6Hz)；FT-IR(KBr，cm -1)：3344，2961，1492，1031；ESI-MS(m/z，％)：318.2(M ++H)； 13CNMR(75MHz，CDCl 3)：δ18.37，19.18，22.53，30.25，56.12，60.11，78.99，128.69，130.03，133.90，137.04；HRMS?for?C 15H 24NO 2SClNa(M ++Na)：calcd.340.1108，found：340.1113.
Embodiment 9
3i's is synthetic
Operate the same, productive rate 70%.
Figure A20051002724900101
3i[α] D 20＝-26.7°(c0.75，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.93(d，6H，J＝6.9Hz)，1.20(s，9H)，1.45(m，1H)，2.35(d，1H，J＝5.1Hz)，3.58(m，1H)，3.84(d，1H，J＝6.6Hz)，4.41(dd，1H，J＝6.6，4.5Hz)，7.30(d，2H，J＝8.4Hz)，7.45(d，2H，J＝8.4Hz)；FT-IR(KBr，cm -1)：3340，2958，1487，1031；ESI-MS(m/z，％)：362.3(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ18.37，19.18，22.52，30.25，56.13，60.16，78.98，122.07，130.36，131.60，137.61；HRMS?for?C 15H 24NO 2SBrNa(M ++Na)：calcd.384.0603，found：384.0614.
Embodiment 10
3j's is synthetic
Operate the same, productive rate 82%.
Figure A20051002724900102
3j[α] D 20＝-40.0°(c0.60，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.92(d，6H，J＝6.6Hz)，1.19(s，9H)，1.46(m，1H)，2.29(s，3H)，2.33(br，1H)，3.56(br，1H)，3.78(d，1H，J＝6.0Hz)，4.45(m，1H)，7.04(d，2H，J＝8.4Hz)，7.41(d，2H，J＝8.4Hz)；FT-IR(KBr，cm -1)：3298，3177，2961，1768，1749，1507，1370，1222，1199，1058，1003；ESI-MS(m/z，％)：342.1(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ18.29，19.23，21.09，22.53，30.07，56.03，60.03，78.77，121.52，129.69，136.07，150.23，169.36；HRMS?for?C 17H 27NO 4SNa(M ++Na)：calcd.361.1553，found：364.1547.
Embodiment 11
3k's is synthetic
Operate the same, productive rate 84%.
Figure A20051002724900103
3k[α] D 20＝-38.1°(c1.55，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.94(s，3H)，0.97(s，3H，)，1.22(s，9H)，1.25-1.29(m，1H)，2.06(d，1H，J＝4.2Hz)，3.63(m，2H)，3.80(s，3H)，4.45(t，1H，J＝4.8Hz)，6.89(d，2H，J＝8.7Hz)，7.34(d，2H，J＝8.7Hz)；
FT-IR(KBr，cm -1)：3504，3139，2962，1515，1247，1039，1001；ESI-MS(m/z，％)：314(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ18.23，19.20，22.49，30.13，55.07，55.91，60.19，78.87，113.81，129.65，130.51，159.15；HRMS?for?C16H27NO3SNa(M ++Na)：calcd.336.1609，found：336.1607.
Embodiment 12
31 synthesize
Operate the same, productive rate 90%.
31[α] D 20＝-35.2°(c0.55，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.96(s，3H)，0.99(s，3H，)，1.24(s，9H)，2.01(d，1H，J＝4.2Hz)，3.59-3.64(m，2H)，3.90(s，3H)，4.43(dd，1H，J＝5.1，9.6Hz)，6.86(dd，1H，J＝6.0，8.7Hz)，6.99(dd，2H，J＝4.8，8.7Hz)；FT-IR(KBr，cm -1)：3428，2960，2837，1522，1041，1025；ESI-MS(m/z，％)：344(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ18.07，19.29，22.46，30.06，55.66，55.80，55.88，60.52，78.77，110.93，111.79，120.71，130.98，148.69；HRMS?for?C17H29NO4SNa(M ++Na)：calcd.366.1709，found：366.1712.
Embodiment 13
3m's is synthetic
Operate the same, productive rate 73%.
3m[α] D 20＝-49.6°(c0.70，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.93(d，3H，J＝6.6Hz)，0.97(d，3H，J＝6.6Hz)，1.22(s，9H)，1.73-1.80(m，1H)，1.94(s，1H)，3.68(s，1H)，3.79(s，3H)，3.84(s，3H)，4.13(dd，1H，J＝7.5，16Hz)，4.47(dd，1H，J＝7.5，15Hz)，6.46-6.49(m，2H)，7.27(dd，1H，J＝3.6，8.7Hz)；FT-IR(KBr，cm -1)：3541，2964，1612，1071；ESI-MS(m/z，％)：344.2(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ16.31，19.74，22.49，29.67，55.21，55.33，55.77，59.17，78.10，99.12，104.47，119.77，130.95，157.93，160.48；HRMS?for?C 17H 29NO 4SNa(M ++Na)：calcd.366.1709，found：366.1706.
Embodiment 14
3n's is synthetic
Operate the same, productive rate 88%.
Figure A20051002724900121
3n[α] D 20＝-62.8°(c0.50，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.91-0.97(m，9H)，1.09(d，3H，J＝5.1Hz)，1.26(s，9H)，1.66(d，1H，J＝4.8Hz)，1.91-1.95(m，1H)，2.20-2.25(m，1H)，3.16-3.20(m，1H)，3.23(d，1H，J＝6.6，Hz)，3.34(d，1H，J＝6.0Hz)；FT-IR(KBr，cm -1)：3367，2964，2874，1473，1035；ESI-MS(m/z，％)：250.2(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ16.62，16.79，19.81，20.87，22.70，27.25，29.28，56.10，62.70，78.15；HRMS?for?C12H27NO2SNa(M ++Na)：calcd.272.1654，found：272.1657.
Embodiment 15
3o's is synthetic
Operate the same, productive rate 87%.
Figure A20051002724900122
3o[α] D 20＝-118.8°(c0.30，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.68(d，3H，J＝6.9Hz)，0.98(d，3H，J＝6.9Hz)，1.26(s，9H)，1.66-1.68(m，1H)，1.91-2.05(m，2H)，2.64-2.69(m，1H)，2.87-2.89(m，1H)，3.20(dd，2H，J＝2.1，9.0Hz)，3.31-3.38(m，2H)，7.18-7.32(m，5H)；FT-IR(KBr，cm -1)：3370，2959，5870，1042；ESI-MS(m/z，％)：312.2(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ18.64，19.69，22.72，28.55，30.25，31.66，55.68，58.09，80.35，125.90，128.35，128.55，141.51；HRMS?C 17H 29NO 2SNa(M ++Na)：calcd.334.1811，found：334.1813.
Embodiment 16
3p's is synthetic
Operate the same, productive rate 95%.
Figure A20051002724900123
3p[α] D 20＝-99.6°(c0.50，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.89(dd，6H，J＝3.9，6.3Hz)，1.02(d，3H，J＝6.3Hz)，1.26(s，9H)，1.27-1.34(m，4H)，1.54-1.75(m，4H)，2.87(s，1H)，3.17
(d，1H，J＝3.9Hz)，3.24(t，1H，J＝6.6，Hz)，3.35-3.39(m，1H)；FT-IR(KBr，cm -1)：3303，3207，2958，1058，1038，998；ESI-MS(m/z，％)：278.2(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ14.00，19.02，19.58，22.46，22.64，25.49，26.88，30.43，31.60，55.59，58.74，79.99；HRMS?for?C14H31NO2SNa(M ++Na)：calcd.300.1968，found：300.1970.
Embodiment 17
Synthesizing of the enantiomer of 3a (ent-3a)
In 25mL Schlenk bottle, tetrahydrofuran (THF) (THF) solution (5mL) of 1.0mmol samarium diodide (SmI2) is cooled to-78 ℃, drip corresponding (the S)-chiral imines of 0.5mmol, 1.0mmol 6mL tetrahydrofuran (THF) (THF) solution of the corresponding aldehyde and the 1.0mmol trimethyl carbinol, reacted 2～4 hours, the cancellation of 5mL saturated aqueous sodium thiosulfate, ethyl acetate extraction, the saturated common salt water washing, anhydrous sodium sulfate drying concentrates, quick purification by silica gel column chromatography, obtain the diastereomer of corresponding cross-coupling product 3a, productive rate 90%, diastereomer ratio (dr) is＞99: 1.
Figure A20051002724900131
ent-3a[α] D 20＝+47.5°(c0.75，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.95(d，3H，J＝5.1Hz)，0.97(d，3H，J＝5.1Hz)，1.22(s，9H)，1.49(m，1H)，2.07(br，1H)，2.33(s，3H)，3.63(br，1H)，3.69(d，1H，J＝5.7Hz)，4.45(t，1H，J＝4.8Hz)，7.14(d，2H，J＝8.1Hz)，7.30(d，2H，J＝8.1Hz)；FT-IR(KBr，cm -1)：3348，1465，1035；ESI-MS(m/z，％)：298.3(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ18.26，19.32，21.10，22.56，30.17，55.95，60.42，78.84，128.39，129.31，135.39，137.87；HRMS?for?C 16H 27NO 2SNa(M ++Na)：calcd.320.1655，found：320.1634.
Embodiment 18
Synthesizing of the enantiomer of 3b (ent-3b)
With corresponding (S)-chiral imines is reaction substrate, operate the same, productive rate 87%, diastereomer ratio (dr) is 99: 1.
Figure A20051002724900132
ent-3b[α] D 20＝+53.2°(c1.20，CHCl 3). 1H?NMR(300MHz，CDCl 3)：δ1.24(d，6H，J＝7.2Hz)，1.24-1.27(m，4H)，1.71-1.91(m，6H)，2.34(s，3H)，3.66(dd，1H，J＝4.2，7.2Hz)，
3.76(d，1H，J＝5.7Hz)，4.48(t，1H，J＝4.9Hz)，7.14(d，2H，J＝8.0Hz)，7.28(d，2H，J＝8.0Hz)；FT-IR(KBr，cm -1)：3348，1463，1032；ESI-MS(m/z，％)：338(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ21.14，22.62，25.59，25.88，26.33，28.28，29.56，39.67，56.04，60.01，78.05，128.38，129.37，135.56，137.81；HRMS?for?C19H31NO2SNa(M ++Na)：calcd.360.1967，found：360.1974.
Embodiment 19
Synthesizing of the enantiomer of 3c (ent-3c)
With corresponding (S)-chiral imines is reaction substrate, operate the same, productive rate 76%, diastereomer ratio (dr) is＞99: 1.
ent-3c[α] D 20＝+35.6°(c1.00，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.85(q，6H，J＝3.0Hz)，1.19(s，9H)，1.20-1.55(m，5H)，1.76(br，1H)，2.33(s，3H)，3.63(d，1H，J＝5.4Hz)，3.84(br，1H，)，4.45(t，1H，J＝5.4Hz)，7.14(d，2H，J＝8.1Hz)，7.28(d，2H，J＝8.1Hz)；FT-IR(KBr，cm -1)：3375，3340，1465，1031；ESI-MS(m/z，％)：326.3(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ10.49，10.60，20.01，21.10，21.28，22.59，41.68，56.01，60.43，74.90，128.28，129.38，135.75，137.85；HRMS?for?C 18H 31NO 2SNa(M ++Na)：calcd.348.1968，found：348.1989.
Embodiment 20
Synthesizing of chirality beta-alkamine
Figure A20051002724900142
The compound 3a (0.2mmol) that obtains in the foregoing description 1 is dissolved in the 2.0mL methyl alcohol, adds 0.5mL 4N HCl in 1,4-dioxane (2.0mmol), reacted 30 minutes, and concentrated, the gained solid mixed solvent recrystallization of methyl alcohol and ether, obtain white solid product, yield 91%.
1H?NMR(300MHz，CDCl 3)：δ0.91(d，3H，J＝6.6Hz)，0.94(d，3H，J＝6.6Hz)，1.24-1.29(m，1H)，2.35(s，3H)，3.56(dd，1H，J＝3.3，8.4Hz)，4.35(d，lH，J＝3.0
Hz)，7.23(d，2H，J＝7.8Hz)，7.45(d，2H，J＝7.8Hz)；FT-IR(KBr，cm -1)：3361，3017，2924，1606，1496；ESI-MS(m/z，％)：194，195(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ19.11，19.38，21.23，32.32，58.03，77.93，130.28，130.39，132.10，140.37；HRMS?C 12H 20NO(M ++H)：calcd.194.1539，found：194.1539.
Embodiment 21
Synthesizing of chirality beta-alkamine
Operate the same, productive rate 92%.
1H?NMR(300MHz，CDCl 3)：δ0.79(d，3H，J＝7.8Hz)，0.84(d，3H，J＝7.8Hz)，1.01-1.04(m，1H)，1.29-1.52(m，4H)，2.35(s，3H)，3.89(dd，1H，J＝3.0，9.3Hz)，4.36(d，1H，J＝3.0Hz)，7.23(d，2H，J＝8.1Hz)，7.46(d，2H，J＝8.1Hz)； 13C?NMR(75MHz，CDCl 3)：δ10.24，10.32，20.77，21.28，43.66，58.03，73.33，130.33，130.35，132.75，140.24.
Embodiment 22
Synthesizing of chirality beta-alkamine
Figure A20051002724900152
Operate the same, productive rate 80%.
1H?NMR(300MHz，CDCl 3)：δ0.96-1.77(m，10H)，2.38(s，3H)，3.61(m，1H)，4.37(d，1H，J＝9.0Hz)，7.26(d，2H，J＝8.4Hz)，7.45(d，2H，J＝8.4Hz)；FT-IR(KBr，cm -1)：3360，3023，2925，2853，1500，1032；ESI-MS(m/z，％)：234，235(M ++H)； 13CNMR(75MHz，CDCl 3)：δ21.27，26.69，26.74，27.38，29.96，30.33，41.69，57.63，76.58，130.23，130.39，132.11，140.28；HRMS?C 15H 24NO(M ++H)：calcd.234.1852，found：234.1853
Embodiment 23
The ethanoyl product of chirality beta-alkamine is synthetic
In the 5mL methylene dichloride, add the amino alcohol product that obtains among the 0.2mmol embodiment 17, the 2mmol triethylamine produces a large amount of white cigarettes, stirs to become settled solution in ten minutes, adds the 2mmol diacetyl oxide, the DMAP of catalytic amount, stirred overnight at room temperature.With the 3mL washing, the NaCl saturated aqueous solution is washed, and anhydrous sodium sulfate drying, rapid column chromatography obtain the product of diacetyl, yield 91%.
[α] D 20＝+153.6(c0.17，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.91(d，3H，J＝6.6Hz)，0.99(d，3H，J＝6.6Hz)，1.77-1.83(m，1H)，1.91(s，3H)，1.94(s，3H)，2.32(s，3H)，4.99(dd，1H，J＝6.6，12.6Hz)，5.22(dd，1H，J＝5.4，8.7Hz)，6.39(d，1H，J＝8.7Hz)，7.12(d，2H，J＝8.1Hz)，7.19(d，2H，J＝8.1Hz)；ESI-MS(m/z，％)：278(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ17.59，19.47，20.77，21.05，23.29，29.24，53.80，79.88，127.72，129.02，135.35，137.33，169.08，171.14；HRMS?C 16H 23NO 3Na(M ++Na)：calcd.300.1570，found：300.1573.
Embodiment 24
The ethanoyl product of chirality beta-alkamine is synthetic
Figure A20051002724900162
Operate the same, productive rate 85%.
[α] D 20＝+127.2(c0.24，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ0.81-1.22(m，6H)，1.43-1.55(m，5H)，1.93(s，3H)，1.96(s，3H)，2.34(s，3H)，5.17(dd，1H，J＝5.7，8.1Hz)，5.26(dd，1H，J＝5.7，8.1Hz)，6.16(d，1H，J＝7.2Hz)，7.13(d，2H，J＝8.1Hz)，7.18(d，2H，J＝8.1Hz)；FT-IR(KBr，cm -1)：3271，2964，1737，1651，1519，1240；ESI-MS(m/z，％)：306(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ10.58，10.91，20.63，20.74，21.01，21.64，23.20，53.67，77.42，127.73，128.91，135.50，137.15，169.05，
170.95；HRMS?C 18H 27NO 3Na(M ++Na)：calcd.328.1883，found：328.1884.
Embodiment 25
The ethanoyl product of chirality beta-alkamine is synthetic
Figure A20051002724900171
Operate the same, productive rate 98%.
[α] D 20＝+116.3(c0.13，CHCl 3)； 1H?NMR(300MHz，CDCl 3)：δ1.00-1.78(m，11H)，1.89(d，3H，J＝3.0Hz)，1.93(d，3H，J＝3.0Hz)，2.27(s，3H)，4.95(dd，1H，J＝4.8，7.2Hz)，5.20(dd，1H，J＝4.8，8.4Hz)，6.35(s，1H)，7.07(d，2H，J＝8.1Hz)，7.13(d，2H，J＝8.1Hz)；ESI-MS(m/z，％)：318(M ++H)； 13C?NMR(75MHz，CDCl 3)：δ20.80，21.05，23.29，25.55，25.71，26.06，27.87，29.65，38.64，53.26，79.41，127.75，129.02；HRMS?C 19H 28NO 3(M ++H)：calcd.318.2064，found：318.2063.

Claims (5)

1. high-optical-purity chiral beta-alkamine compound, its structural formula is as follows:
Figure A2005100272490002C1
Perhaps
Figure A2005100272490002C2
R wherein 1=C 1-16Straight chain, have the alkyl of side chain or aryl or C 3-6Cycloalkyl; R 2=C 1-12Straight chain, have the alkyl of side chain or aryl, C 3-6Cycloalkyl, or R 3Or R 4The phenyl that replaces; R 3Or R 4=H, C 1-6Alkyl, halogen, C 1-6Alkoxyl group or OCOR 5Described halogen is F, Cl or Br; R 5=C 1-6Alkyl.
2. the preparation method of a high-optical-purity chiral beta-alkamine compound as claimed in claim 1 is characterized in that with structural formula being
Figure A2005100272490002C3
Aldehyde and structural formula be Perhaps
Figure A2005100272490002C5
Chirality N-tertiary butyl sulfenimide, under-78 ℃, as reaction reagent, as organic solvent, cross-coupling reaction takes place 1-20 hour with tetrahydrofuran (THF) with samarium diodide in the presence of the trimethyl carbinol or methyl alcohol; R wherein 1And R 2According to claim 1, the mol ratio of described aldehyde, chirality N-tertiary butyl sulfenimide, samarium diodide, the trimethyl carbinol or methyl alcohol is respectively: 1.0: 1.0～3.0: 1.5～2.2: 1.5～2.2.
3. the preparation method of a kind of high-optical-purity chiral beta-alkamine compound as claimed in claim 2 is characterized in that described imines is a chirality N-tertiary butyl sulfenimide.
4. the purposes of a high-optical-purity chiral beta-alkamine compound as claimed in claim 1 is characterized in that being used to prepare structural formula is Perhaps The chirality beta-alkamine, R wherein 1And R 2According to claim 1.
5. the purposes of high-optical-purity chiral beta-alkamine compound as claimed in claim 4 is characterized in that chiral beta-alkamine compound as claimed in claim 1 reacted 1-10 hour, removed N-tertiary butyl sulfinyl under acidic conditions.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104974049B (en) * 2014-04-09 2016-08-31 中国科学院化学研究所 One prepares 1, the method for 5-amino alcohol

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